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PRENOME 40 MG GASTRO-RESISTANT CAPSULES HARD

Active substance(s): OMEPRAZOLE / OMEPRAZOLE / OMEPRAZOLE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Prenome 40 mg gastro-resistant capsules, hard

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 40 mg omeprazole.
Excipient(s) with known effect:
Each capsule contains approximately 75.20 – 86.01 mg sucrose.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Gastro-resistant capsule, hard (gastro-resistant capsule).
Opaque white hard gelatine capsule (size #1) printed “OM 40”, containing spherical
pellets.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Prenome is indicated in:
Adults


Treatment of duodenal ulcers



Prevention of relapse of duodenal ulcers



Treatment of gastric ulcers



Prevention of relapse of gastric ulcers



In combination with appropriate antibiotics, Helicobacter pylori (H. pylori)
eradication in peptic ulcer disease



Treatment of NSAID-associated gastric and duodenal ulcers



Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk



Treatment of reflux esophagitis



Long-term management of patients with healed reflux esophagitis



Treatment of symptomatic gastro-esophageal reflux disease



Treatment of Zollinger-Ellison syndrome
Children aged over 1 year and ≥ 10 kg



Treatment of reflux esophagitis



Symptomatic treatment of heartburn and acid regurgitation in gastro-esophageal
reflux disease
Children aged over 4 years and adolescents



4.2

In combination with antibiotics in treatment of duodenal ulcer caused by H. pylori

Posology and method of administration
Posology
Treatment of duodenal ulcers
The recommended dose in patients with an active duodenal ulcer is Prenome 20 mg
once daily. In most patients healing occurs within two weeks. For those patients who
may not be fully healed after the initial course, healing usually occurs during a further
two weeks treatment period. In patients with poorly responsive duodenal ulcer
Prenome 40 mg once daily is recommended and healing is usually achieved within
four weeks.
Prevention of relapse of duodenal ulcers
For the prevention of relapse of duodenal ulcer in H. pylori negative patients or when
H. pylori eradication is not possible the recommended dose is Prenome 20 mg once
daily. In some patients a daily dose of 10 mg may be sufficient. In case of therapy
failure, the dose can be increased to 40 mg.
Treatment of gastric ulcers
The recommended dose is Prenome 20 mg once daily. In most patients healing occurs
within four weeks. For those patients who may not be fully healed after the initial
course, healing usually occurs during a further four weeks treatment period. In

patients with poorly responsive gastric ulcer Prenome 40 mg once daily is
recommended and healing is usually achieved within eight weeks.
Prevention of relapse of gastric ulcers
For the prevention of relapse in patients with poorly responsive gastric ulcer the
recommended dose is Prenome 20 mg once daily. If needed the dose can be increased
to Prenome 40 mg once daily.
H. pylori eradication in peptic ulcer disease
For the eradication of H. pylori the selection of antibiotics should consider the
individual patient’s drug tolerance, and should be undertaken in accordance with
national, regional and local resistance patterns and treatment guidelines.


Prenome 20 mg + clarithromycin 500 mg + amoxicillin 1,000 mg, each twice daily
for one week, or



Prenome 20 mg + clarithromycin 250 mg (alternatively 500 mg) + metronidazole 400
mg (or 500 mg or tinidazole 500 mg), each twice daily for one week or



Prenome 40 mg once daily with amoxicillin 500 mg and metronidazole 400 mg (or
500 mg or tinidazole 500 mg), both three times a day for one week.
In each regimen, if the patient is still H. pylori positive, therapy may be repeated.
Treatment of NSAID-associated gastric and duodenal ulcers
For the treatment of NSAID-associated gastric and duodenal ulcers, the
recommended dose is Prenome 20 mg once daily. In most patients healing occurs
within four weeks. For those patients who may not be fully healed after the initial
course, healing usually occurs during a further four weeks treatment period.
Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk
For the prevention of NSAID-associated gastric ulcers or duodenal ulcers in patients
at risk (age> 60, previous history of gastric and duodenal ulcers, previous history of
upper GI bleeding) the recommended dose is Prenome 20 mg once daily.
Treatment of reflux esophagitis
The recommended dose is Prenome 20 mg once daily. In most patients healing occurs
within four weeks. For those patients who may not be fully healed after the initial
course, healing usually occurs during a further four weeks treatment period.
In patients with severe esophagitis Prenome 40 mg once daily is recommended and
healing is usually achieved within eight weeks.
Long-term management of patients with healed reflux esophagitis

For the long-term management of patients with healed reflux esophagitis the
recommended dose is Prenome 10 mg once daily. If needed, the dose can be
increased to Prenome 20-40 mg once daily.
Treatment of symptomatic gastro-esophageal reflux disease
The recommended dose is Prenome 20 mg daily. Patients may respond adequately to
10 mg daily, and therefore individual dose adjustment should be considered.
If symptom control has not been achieved after four weeks treatment with Prenome
20 mg daily, further investigation is recommended.
Treatment of Zollinger-Ellison syndrome
In patients with Zollinger-Ellison syndrome the dose should be individually adjusted
and treatment continued as long as clinically indicated. The recommended initial dose
is Prenome 60 mg daily. All patients with severe disease and inadequate response to
other therapies have been effectively controlled and more than 90% of the patients
maintained on doses of Prenome 20-120 mg daily. When dose exceed Prenome 80 mg
daily, the dose should be divided and given twice daily.
Pediatric population
Children aged over 1 year and ≥ 10 kg
Treatment of reflux esophagitis
Symptomatic treatment of heartburn and acid regurgitation in gastro-esophageal
reflux disease
The posology recommendations are as follows:
Age

Weight

Posology

≥ 1 year of

10-20 kg

10 mg once daily. The dose can be increased to 20
mg once daily if needed

> 20 kg

20 mg once daily. The dose can be increased to 40
mg once daily if needed

age

≥ 2 years of
age

Reflux esophagitis: The treatment time is 4-8 weeks.
Symptomatic treatment of heartburn and acid regurgitation in gastro-esophageal
reflux disease: The treatment time is 2–4 weeks. If symptom control has not been
achieved after 2–4 weeks the patient should be investigated further.
Children aged over 4 years and adolescents
Treatment of duodenal ulcer caused by H. pylori
When selecting appropriate combination therapy, consideration should be given to
official national, regional and local guidance regarding bacterial resistance, duration

of treatment (most commonly 7 days but sometimes up to 14 days), and appropriate
use of antibacterial agents.
The treatment should be supervised by a specialist.
The posology recommendations are as follows:
Weight

Posology

15–30 kg

Combination with two antibiotics: Prenome 10 mg, amoxicillin 25
mg/kg body weight and clarithromycin 7.5 mg/kg body weight are
all administrated together two times daily for one week.

31–40 kg

Combination with two antibiotics: Prenome 20 mg, amoxicillin 750
mg and clarithromycin 7.5 mg/kg body weight are all administrated
two times daily for one week.

> 40 kg

Combination with two antibiotics: Prenome 20 mg, amoxicillin 1 g
and clarithromycin
500 mg are all administrated two times daily for one week.

Patients with renal impairment
Dose adjustment is not needed in patients with impaired renal function (see section
5.2).
Patients with hepatic impairment
In patients with impaired hepatic function a daily dose of 10–20 mg may be sufficient
(see section 5.2).
Older people (> 65 years old)
Dose adjustment is not needed in the elderly (see section 5.2).
Method of administration
It is recommended to take Prenome capsules in the morning, swallowed whole with
half a glass of water. The capsules must not be chewed or crushed.
For patients with swallowing difficulties and for children who can drink or swallow
semi-solid food
Patients can open the capsule and swallow the contents with half a glass of water or
after mixing the contents in a slightly acidic fluid e.g., fruit juice or applesauce, or in
non-carbonated water. Patients should be advised that the dispersion should be taken
immediately (or within 30 minutes) and always be stirred just before drinking and
rinsed down with half a glass of water.
Alternatively patients can suck the capsule and swallow the pellets with half a glass
of water. The enteric-coated pellets must not be chewed.

4.3

Contraindications
Hypersensitivity to the active substance(s), substituted benzimidazoles or to any of
the excipients listed in section 6.1.
Omeprazole like other proton pump inhibitors (PPIs) must not be used concomitantly
with nelfinavir (see section 4.5).

4.4

Special warnings and precautions for use
In the presence of any alarm symptom (e.g. significant unintentional weight loss,
recurrent vomiting, dysphagia, haematemesis or melena) and when gastric ulcer is
suspected or present, malignancy should be excluded, as treatment may alleviate
symptoms and delay diagnosis.
Co-administration of atazanavir with proton pump inhibitors is not recommended (see
section 4.5). If the combination of atazanavir with a proton pump inhibitor is judged
unavoidable, close clinical monitoring (e.g virus load) is recommended in
combination with an increase in the dose of atazanavir to 400 mg with 100 mg of
ritonavir; omeprazole 20 mg should not be exceeded.
Omeprazole, as all acid-blocking medicines, may reduce the absorption of vitamin
B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in
patients with reduced body stores or risk factors for reduced vitamin B12 absorption
on long-term therapy.
Omeprazole is a CYP2C19 inhibitor. When starting or ending treatment with
omeprazole, the potential for interactions with drugs metabolised through CYP2C19
should be considered. An interaction is observed between clopidogrel and omeprazole
(see section 4.5). The clinical relevance of this interaction is uncertain. As a
precaution, concomitant use of omeprazole and clopidogrel should be discouraged.
Hypomagnesaemia
Severe hypomagnesaemia has been reported in patients treated with proton pump
inhibitors (PPIs) like omeprazole for at least three months, and in most cases for a
year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium,
convulsions, dizziness and ventricular arrhythmia can occur but they may begin
insidiously and be overlooked. In most affected patients, hypomagnesaemia improved
after magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with digoxin or
drugs that may cause hypomagnesaemia (e.g. diuretics), healthcare professionals

should consider measuring magnesium levels before starting PPI treatment and
periodically during treatment.

Risk of fractures of the hip, wrist and spine
Proton pump inhibitors, especially if used in high doses and over long durations (>1
year), may modestly increase the risk of hip, wrist and spine fracture, predominantly
in the elderly or in presence of other recognised risk factors. Observational studies
suggest that proton pump inhibitors may increase the overall risk of fracture by 1040%. Some of this increase may be due to other risk factors.
Patients at risk of osteoporosis should receive care according to current clinical
guidelines and they should have an adequate intake of vitamin D and calcium.
Interference with laboratory tests
Increased Cromogranin A (CgA) level may interfere with investigations for
neuroendocrine tumours. To avoid this interference the omeprazole treatment should
be stopped for at least five days before CgA measurements (see section 5.1).
Some children with chronic illnesses may require long-term treatment although it is
not recommended.
Prenome contains sucrose. Patients with rare hereditary problems of fructose
intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency
should not take this medicine.
Treatment with proton pump inhibitors may lead to slightly increased risk of
gastrointestinal infections such as Salmonella and Campylobacter (see section 5.1).
As in all long-term treatments, especially when exceeding a treatment period of 1
year, patients should be kept under regular surveillance.

4.5

Interaction with other medicinal products and other forms of interaction
Effects of omeprazole on the pharmacokinetics of other active substances
Active substances with pH dependent absorption
The decreased intragastric acidity during treatment with omeprazole might increase or
decrease the absorption of active substances with a gastric pH dependent absorption.
Nelfinavir, atazanavir

The plasma levels of nelfinavir and atazanavir are decreased in case of coadministration with omeprazole.
Concomitant administration of omeprazole with nelfinavir is contraindicated (see
section 4.3).
Co-administration of omeprazole (40 mg once daily) reduced mean nelvinavir
exposure by ca. 40% and the mean exposure of the pharmacologically active
metabolite M8 was reduced by ca. 75 –90%. The interaction may also involve
CYP2C19 inhibition.
Concomitant administration of omeprazole with atazanavir is not recommended (see
section 4.4).
Concomitant administration of omeprazole (40 mg once daily) and atazanavir 300
mg/ritonavir 100 mg to healthy volunteers resulted in a 75% decrease of the
atazanavir exposure. Increasing the atazanavir dose to 400 mg did not compensate for
the impact of omeprazole on atazanavir exposure. The co-administration of
omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg to healthy
volunteers resulted in a decrease of approximately 30% in the atazanavir exposure as
compared to atazanavir 300 mg/ritonavir 100 mg once daily.
Digoxin
Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy
subjects increased the bioavailability of digoxin by 10%. Digoxin toxicity has been
rarely reported. However caution should be exercised when omeprazole is given at
high doses in elderly patients. Therapeutic drug monitoring of digoxin should be then
be reinforced.
Clopidogrel
Results from studies in healthy subjects have shown a pharmacokinetic
(PK)/pharmacodynamic (PD) interaction between clopidogrel (300 mg loading
dose/75 mg daily maintenance dose) and omeprazole (80 mg p.o. daily) resulting in a
decreased exposure to the active metabolite of clopidogrel by an average of 46% and
a decreased maximum inhibition of (ADP induced) platelet aggregation by an average
of 16%.
Inconsistent data on the clinical implications of a PK/PD interaction of omeprazole in
terms of major cardiovascular events have been reported from both observational and
clinical studies. As a precaution, concomitant use of omeprazole and clopidogrel
should be discouraged (see section 4.4).
Other active substances
The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is
significantly reduced and thus clinical efficacy may be impaired. For posaconazole
and erlotinib concomitant use should be avoided.
Active substances metabolised by CYP2C19

Omeprazole is a moderate inhibitor of CYP2C19, the major omeprazole metabolising
enzyme. Thus, the metabolism of concomitant active substances also metabolised by
CYP2C19, may be decreased and the systemic exposure to these substances
increased. Examples of such drugs are R-warfarin and other vitamin K antagonists,
cilostazol, diazepam and phenytoin.

Cilostazol
Omeprazole, given in doses of 40 mg to healthy subjects in a cross-over study,
increased Cmax and AUC for cilostazol by 18% and 26% respectively, and one of its
active metabolites by 29% and 69% respectively.
Phenytoin
Monitoring phenytoin plasma concentration is recommended during the first two
weeks after initiating omeprazole treatment and, if a phenytoin dose adjustment is
made, monitoring and a further dose adjustment should occur upon ending
omeprazole treatment.
Unknown mechanism
Saquinavir
Concomitant administration of omeprazole with saquinavir/ritonavir resulted in
increased plasma levels up to approximately 70% for saquinavir associated with good
tolerability in HIV-infected patients.
Tacrolimus
Concomitant administration of omeprazole has been reported to increase the serum
levels of tacrolimus. A reinforced monitoring of tacrolimus concentrations as well as
renal function (creatinine clearance) should be performed, and dosage of tacrolimus
adjusted if needed.
Methotrexate
When given together with proton-pump inhibitors, methotrexate levels have been
reported to increase in some patients. In high-dose methotrexate administration a
temporary withdrawal of omeprazole may need to be considered.
Effects of other active substances on the pharmacokinetics of omeprazole
Inhibitors CYP2C19 and/or CYP3A4
Since omeprazole is metabolised by CYP2C19 and CYP3A4, active substances
known to inhibit CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole)
may lead to increased omeprazole serum levels by decreasing omeprazole’s rate of
metabolism. Concomitant voriconazole treatment resulted in more than doubling of
the omeprazole exposure. As high doses of omeprazole have been well-tolerated

adjustment of the omeprazole dose is not generally required. However, dose
adjustment should be considered in patients with severe hepatic impairment and if
long-term treatment is indicated.

Inducers of CYP2C19 and/or CYP3A4
Active substances known to induce CYP2C19 or CYP3A4 or both (such as rifampicin
and St John’s wort) may lead to decreased omeprazole serum levels by increasing
omeprazole’s rate of metabolism.

4.6

Fertility, pregnancy and lactation
Pregnancy
Results from three prospective epidemiological studies (more than 1000 exposed
outcomes) indicate no adverse effects of omeprazole on pregnancy or on the health of
the foetus/newborn child. Omeprazole can be used during pregnancy.

Breastfeeding
Omeprazole is excreted in breast milk but is not likely to influence the child when
therapeutic doses are used.
Fertility
Animal studies with the racemic mixture omeprazole, given by oral administration do
not indicate effects with respect to fertility.

4.7

Effects on ability to drive and use machines
Prenome is not likely to affect the ability to drive or use machines. Adverse drug
reactions such as dizziness and visual disturbances may occur (see section 4.8). If
affected, patients should not drive or operate machinery.

4.8

Undesirable effects
The most common side effects (1-10% of patients) are headache, abdominal pain,
constipation, diarrhoea, flatulence and nausea/vomiting.
The following adverse drug reactions have been identified or suspected in the clinical
trials programme for omeprazole and post-marketing. None was found to be doserelated. Adverse reactions listed below are classified according to frequency and
System Organ Class (SOC). Frequency categories are defined according to the
following convention: Very common (≥ 1/10), Common (≥ 1/100 to < 1/10),

Uncommon (≥ 1/1,000 to < 1/100), Rare (≥ 1/10,000 to < 1/1,000), Very rare (<
1/10,000), Not known (cannot be estimated from the available data).

SOC/frequency
Adverse reaction
Blood and lymphatic system disorders
Rare:
Leukopenia, thrombocytopenia
Very rare:
Agranulocytosis, pancytopenia
Immune system disorders
Rare:
Hypersensitivity reactions e.g. fever, angioedema and
anaphylactic reaction/shock
Metabolism and nutrition disorders
Rare:
Hyponatraemia
Not known:
Hypomagnesaemia; severe hypomagnesaemia may
result in hypocalcaemia
Hypomagnesaemia may also be associated with
hypokalaemia.
Psychiatric disorders
Uncommon:
Insomnia
Rare:
Agitation, confusion, depression
Very rare:
Aggression, hallucinations
Nervous system disorders
Common:
Headache
Uncommon:
Dizziness, paraesthesia, somnolence
Rare:
Taste disturbance
Eye disorders
Rare:
Blurred vision
Ear and labyrinth disorders
Uncommon:
Vertigo
Respiratory, thoracic and mediastinal disorders
Rare:
Bronchospasm
Gastrointestinal disorders
Common:
Abdominal pain, constipation, diarrhoea, flatulence,
nausea/vomiting, fundic gland polyps (benign)
Rare:
Dry mouth, stomatitis, gastrointestinal candidiasis
Not known:
Microscopic colitis
Hepatobiliary disorders
Uncommon:
Increased liver enzymes
Rare:
Hepatitis with or without jaundice
Very rare:
Hepatic failure, encephalopathy in patients with preexisting liver disease
Skin and subcutaneous tissue disorders
Uncommon:
Dermatitis, pruritus, rash, urticaria
Rare:
Alopecia, photosensitivity
Very rare:
Erythema multiforme, Stevens-Johnson syndrome,
toxic epidermal necrolysis (TEN)
Not known:
Subacute cutaneous lupus erythematosus (see section
4.4).
Musculoskeletal and connective tissue disorders
Uncommon:
Fracture of the hip, wrist or spine

Rare:
Arthralgia, myalgia
Very rare:
Muscular weakness
Renal and urinary disorders
Rare:
Interstitial nephritis
Reproductive system and breast disorders
Very rare:
Gynaecomastia
General disorders and administration site conditions
Uncommon:
Malaise, peripheral oedema
Rare:
Increased sweating
Paediatric population
The safety of omeprazole has been assessed in a total of 310 children aged 0 to 16
years with acid-related disease. There are limited long term safety data from 46
children who received maintenance therapy of omeprazole during a clinical study for
severe erosive esophagitis for up to 749 days. The adverse event profile was generally
the same as for adults in short- as well as in long-term treatment. There are no long
term data regarding the effects of omeprazole treatment on puberty and growth.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard

4.9

Overdose
Symptoms
There is limited information available on the effects of overdoses of omeprazole in
humans. In the literature, doses of up to 560 mg have been described, and occasional
reports have been received when single oral doses have reached up to 2,400 mg
omeprazole (120 times the usual recommended clinical dose). Nausea, vomiting,
dizziness, abdominal pain, diarrhoea and headache have been reported. Also apathy,
depression and confusion have been described in single cases.
The symptoms described have been transient, and no serious outcome has been
reported. The rate of elimination was unchanged (first order kinetics) with increased
doses.
Management
Treatment, if needed, is symptomatic.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Drugs for acid related disorders, proton pump inhibitors,
ATC code: A02BC01
Mechanism of action
Omeprazole, a racemic mixture of two enantiomers reduces gastric acid secretion
through a highly targeted mechanism of action. It is a specific inhibitor of the acid
pump in the parietal cell. It is rapidly acting and provides control through reversible
inhibition of gastric acid secretion with once daily dosing.
Omeprazole is a weak base and is concentrated and converted to the active form in
the highly acidic environment of the intracellular canaliculi within the parietal cell,
where it inhibits the enzyme H+K+-ATPase - the acid pump. This effect on the final
step of the gastric acid formation process is dose-dependent and provides for highly
effective inhibition of both basal acid secretion and stimulated acid secretion,
irrespective of stimulus.
Pharmacodynamic effects
All pharmacodynamic effects observed can be explained by the effect of omeprazole
on acid secretion.
Effect on gastric acid secretion
Oral dosing with omeprazole once daily provides for rapid and effective inhibition of
daytime and nighttime gastric acid secretion with maximum effect being achieved
within 4 days of treatment. With omeprazole 20 mg, a mean decrease of at least 80%
in 24-hour intragastric acidity is then maintained in duodenal ulcer patients, with the
mean decrease in peak acid output after pentagastrin stimulation being about 70% 24
hours after dosing.
Oral dosing with omeprazole 20 mg maintains an intragastric pH of ≥ 3 for a mean
time of 17 hours of the 24-hour period in duodenal ulcer patients.
As a consequence of reduced acid secretion and intragastric acidity, omeprazole dosedependently reduces/normalizes acid exposure of the esophagus in patients with
gastro-esophageal reflux disease.
The inhibition of acid secretion is related to the area under the plasma concentrationtime curve (AUC) of omeprazole and not to the actual plasma concentration at a
given time.
No tachyphylaxis has been observed during treatment with omeprazole.

Effect on H. pylori
H. pylori is associated with peptic ulcer disease, including duodenal and gastric ulcer
disease. H. pylori is a major factor in the development of gastritis. H. pylori together
with gastric acid are major factors in the development of peptic ulcer disease. H.
pylori is a major factor in the development of atrophic gastritis which is associated
with an increased risk of developing gastric cancer.
Eradication of H. pylori with omeprazole and antimicrobials is associated with, high
rates of healing and long-term remission of peptic ulcers.
Dual therapies have been tested and found to be less effective than triple therapies.
They could, however, be considered in cases where known hypersensitivity precludes
use of any triple combination.
Other effects related to acid inhibition
During long-term treatment gastric glandular cysts have been reported in a somewhat
increased frequency. These changes are a physiological consequence of pronounced
inhibition of acid secretion, are benign and appear to be reversible.
Decreased gastric acidity due to any means including proton pump inhibitors,
increases gastric counts of bacteria normally present in the gastrointestinal tract.
Treatment with acid-reducing drugs may lead to slightly increased risk of
gastrointestinal infections such as Salmonella and Campylobacter.
During treatment with antisecretory medicinal products serum gastrin increases in
response to the decreased acid secretion.
Also CgA increases due to decreased gastric acidity. The increased CgA level may
interfere with investigations for neuroendocrine tumours. Literature reports indicate
that proton pump inhibitor treatment should be stopped at least 5 days before CgA
measurement. If CgA and gastrine levels have not normalised after 5 days,
measurements should be repeated 14 days after cessation of omeprazole treatment.
An increased number of ECL cells possibly related to the increased serum gastrin
levels, have been observed in some patients (both children and adults) during long
term treatment with omeprazole. The findings are considered to be of no clinical
significance.
Paediatric population
In a non-controlled study in children (1 to 16 years of age) with severe reflux
esophagitis, omeprazole at doses of 0.7 to 1.4 mg/kg improved esophagitis level in
90% of the cases and significantly reduced reflux symptoms. In a single-blind study,
children aged 0–24 months with clinically diagnosed gastroesophageal reflux disease
were treated with 0.5, 1.0 or 1.5 mg omeprazole/kg. The frequency of
vomiting/regurgitation episodes decreased by 50% after 8 weeks of treatment
irrespective of the dose.

Eradication of H. pylori in children
A randomised, double blind clinical study (Héliot study) concluded that omeprazole
in combination with two antibiotics (amoxicillin and clarithromycin), was safe and
effective in the treatment of H. pylori infection in children age 4 years old and above
with gastritis: H. pylori eradication rate: 74.2% (23/31 patients) with omeprazole +
amoxicillin + clarithromycin versus 9.4% (3/32 patients) with amoxicillin +
clarithromycin. However, there was no evidence of any clinical benefit with respect
to dyspeptic symptoms. This study does not support any information for children
aged less than 4 years.

5.2

Pharmacokinetic properties
Absorption
Omeprazole and omeprazole magnesium are acid labile and are therefore
administered orally as enteric-coated granules in capsules or tablets. Absorption of
omeprazole is rapid, with peak plasma levels occurring approximately 1-2 hours after
dose. Absorption of omeprazole takes place in the small intestine and is usually
completed within 3-6 hours. Concomitant intake of food has no influence on the
bioavailability. The systemic availability (bioavailability) from a single oral dose of
omeprazole is approximately 40%. After repeated once-daily administration, the
bioavailability increases to about 60%.
Distribution
The apparent volume of distribution in healthy subjects is approximately 0.3 l/kg
body weight.
Omeprazole is 97% plasma protein bound.
Biotransformation
Omeprazole is completely metabolised by the cytochrome P450 system (CYP). The
major part of its metabolism is dependent on the polymorphically expressed
CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite
in plasma. The remaining part is dependent on another specific isoform, CYP3A4,
responsible for the formation of omeprazole sulphone. As a consequence of high
affinity of omeprazole to CYP2C19, there is a potential for competitive inhibition and
metabolic drug-drug interactions with other substrates for CYP2C19. However, due
to low affinity to CYP3A4, omeprazole has no potential to inhibit the metabolism of
other CYP3A4 substrates. In addition, omeprazole lacks an inhibitory effect on the
main CYP enzymes.
Approximately 3% of the Caucasian population and 15-20% of Asian populations
lack a functional CYP2C19 enzyme and are called poor metabolisers. In such
individuals the metabolism of omeprazole is probably mainly catalysed by CYP3A4.
After repeated once-daily administration of 20 mg omeprazole, the mean AUC was 5
to 10 times higher in poor metabolisers than in subjects having a functional CYP2C19

enzyme (extensive metabolisers). Mean peak plasma concentrations were also higher,
by 3 to 5 times. These findings have no implications for the posology of omeprazole.
Elimination
The plasma elimination half-life of omeprazole is usually shorter than one hour both
after single and repeated oral once-daily dosing. Omeprazole is completely eliminated
from plasma between doses with no tendency for accumulation during once-daily
administration. Almost 80% of an oral dose of omeprazole is excreted as metabolites
in the urine, the remainder in the faeces, primarily originating from bile secretion.
Linearity/non-linearity
The AUC of omeprazole increases with repeated administration. This increase is
dose-dependent and results in a non-linear dose-AUC relationship after repeated
administration. This time- and dose-dependency is due to a decrease of first pass
metabolism and systemic clearance probably caused by an inhibition of the CYP2C19
enzyme by omeprazole and/or its metabolites (e.g. the sulphone).
No metabolite has been found to have any effect on gastric acid secretion.
Hepatic impairment
The metabolism of omeprazole in patients with liver dysfunction is impaired,
resulting in an increased AUC. Omeprazole has not shown any tendency to
accumulate with once daily dosing.
Renal impairment
The pharmacokinetics of omeprazole, including systemic bioavailability and
elimination rate, are unchanged in patients with reduced renal function.
Older people
The metabolism rate of omeprazole is somewhat reduced in elderly subjects (75-79
years of age).
Paediatric population
During treatment with the recommended doses to children from the age of 1 year,
similar plasma concentrations were obtained as compared to adults. In children
younger than 6 months, clearance of omeprazole is low due to low capacity to
metabolise omeprazole.

5.3

Preclinical safety data
Gastric ECL-cell hyperplasia and carcinoids, have been observed in life-long studies
in rats treated with omeprazole. These changes are the result of sustained
hypergastrinaemia secondary to acid inhibition.

Similar findings have been made after treatment with H2-receptor antagonists, proton
pump inhibitors and after partial fundectomy. Thus, these changes are not from a
direct effect of any individual active substance.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Content:
Sugar Spheres (sucrose and maize starch)
Hypromellose (E-464)
Talc (E-553b)
Titanium dioxide (E-171)
Disodium phosphate dihydrate (E-339 ii)
Sodium lauryl sulphate
Polysorbate 80
Methacrylic acid-ethyl acrylate copolymer
Triethyl Citrate (E-1505)
Capsule shell
Gelatine
Titanium dioxide (E-171)
Printing ink (black iron oxide (E-172), potassium hydroxide and shellac)

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
Bottle: 3 years
Shelf life after first opening of the bottle: 100 days.
Al/Al blister: 18 months
PVC-PVDC/Al blister: 2 years

6.4

Special precautions for storage
Bottle: Does not require any special storage conditions. Keep the container tightly
closed in order to protect from moisture.
Al/Al blister: Store below 30ºC. Store in the original package in order to protect from
moisture.
PVC-PVDC/Al blister: Store below 30ºC. Store in the original package in order to
protect from moisture.

6.5

Nature and contents of container
White HDPE bottle with a cap and a tamper evident ring closure with a desiccant
agent: 14, & 28 capsules.
Al/Al blister: 14 & 28 capsules.
PVC-PVDC/Al blister: 14 & 28 capsules.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER
DISTRIQUIMICA, S.A.
Avda. Mare de Déu de Montserrat. 221
08041 Barcelona - Spain

8

MARKETING AUTHORISATION NUMBER(S)
PL 21562/0012

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
19/02/2015

10

DATE OF REVISION OF THE TEXT
06/05/2016

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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